OBJECTIVE: A unique subset of viruses appear when HIV-1 is transmitted by sexual exposure. These viruses are classified as "monocytotropic" because of their ability to infect monocyte cells in tissues and blood. We are testing whether this type of virus is absolutely required for sexual transmission and also, whether vaccines should be targeted specifically at this virus subtype. RESULTS Studies of recently infected patients showed that HIV-1 strains classified as "monocytotropic" were most abundant early in disease and may have been transmitted most efficiently. We have assessed modified viruses and recombinant simian/ human immunodeficiency viruses to determine their capacity for efficient mucosal transmission in macaques. SHIV carrying HIV envelope sequences from monocytotropic or dual-tropic viruses were transmitted efficiently cross rectal or vaginal mucosal surfaces. Viruses carrying T cell-tropic envelope genes were transmitted poorly across these barriers and established weak and transient infections. We are characterizing additional viruses and the earliest immune responses to mucosal infection in order to identify key mechanisms that link monocytotropism to efficient mucosal transmission. FUTURE DIRECTIONS We are developing in vitro systems that more closely mimic the steps in mucosal virus transmission in vivo. These models will be used increasingly to explore the function of intraepithelial cells and epithelial cells in restricting virus transmission. KEY WORDS AIDS, transmission, vaccine, molecular virology, mucosa Stevenson, Principal Investigator)